The aim of this research program is to investigate the anti- hemostatic and anti-inflammatory compounds in vector saliva that allow efficient blood feeding and enhancement of pathogen transmission. Anti-hemostatic compounds of interest include anti- clotting, anti-platelet and vasodilators. Anti-inflammatory compounds include immunomodulatory compounds as well as compounds that modify effector arms of the immune response, such as anti-complement activity found in the saliva of some ticks. While the vector attempts to modify the feeding site to enhance success of blood feeding, such site becomes locally compromised in its ability to react to injury and becomes an easy site for pathogen invasion. Novel pharmaceuticals and novel targets for vaccine development will be ultimate benefits of this program. In the current year we have discovered a novel nitric oxide carrier protein that is homologous to inositol phosphatase, suggesting this later enzyme may be regulated by NO. We have also discovered a new gene encoding for an apyrase activity, that adenosine is the main vasodilator of Phelebotomus sand flies, and that saliva of this sand fly modifies transmission of Leishmania major, making possible to identify new targets for vaccine development. The vasodilator of Anopheles mosquitoes was also purified and cloned, being a member of the myeloperoxidase family, while that of the black fly was found to be a novel gene. Finally, the kininase of the tick Ixodes dammini was purified and characterized as a member of the angiotensin converting enzyme family.